I am going to answer the sample USMLE Step 1 Questions with Explanation. These questions are available at USMLE.org
Q- A 45-year-old man is brought to the emergency department 30 minutes after the sudden onset of crushing chest pain. His father, maternal aunt, and paternal uncle all died of myocardial infarctions under the age of 50 years. Physical examination shows tendinous xanthomas on the hands and thickened Achilles tendons. Serum lipid studies show a total cholesterol concentration of 410 mg/dL, HDL-cholesterol concentration of 30 mg/dL, and triglyceride concentration of 140 mg/dL. The diagnosis of myocardial infarction is made. This patient most likely has a deficiency of which of the following?
(A) Apo B48
(B) Apo C
(C) HMG-CoA reductase activity
(D) LDL receptor
(E) Lipoprotein lipase activity
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Answer
This is a case of familial hypercholesterolemia (FH), an autosomal dominant disorder caused by a defect in the LDL receptor. A myocardial infarction at 45 years of age, combined with a strong family history of premature myocardial infarctions, is characteristic of FH. Tendinous xanthomas are pathognomonic for FH, arising due to deposition of LDL cholesterol in tendons. A cholesterol level of 410 mg/dL with normal triglycerides and low HDL is a classic lipid profile in FH.
The defect in FH involves a mutation in the LDL receptor gene, which leads to reduced or absent LDL receptor activity. As a result, LDL particles cannot be effectively cleared from the bloodstream, leading to very high plasma LDL cholesterol levels.
The correct answer is D